BACTERIAL SEPSIS AND MENINGITIS - Nizet Laboratory at UCSD

during labor for monitoring of heart rate [85,340,341].
The incidence of this type of infection in the hands of
experienced clinicians is generally quite low (0.1% to
5.2%), however [342]. A 10-year survey of neonatal
enterococcal bacteremia detected 6 of 44 infants with
scalp abscesses as the probable source of their bacteremia
[85]. The investigators were unable to deduce from the
data available whether these abscesses were associated
with fetal scalp monitoring, intravenous infusion, or other
procedures that resulted in loss of the skin barrier.
Transient bacteremia can accompany procedures that
traumatize mucosal membranes such as endotracheal suctioning
[343]. Invasion of the bloodstream also can follow
multiplication of organisms in the upper respiratory tract
or other foci. Although the source of bacteremia frequently
is inapparent, careful inspection can reveal a
focus, such as an infected circumcision site or infection
of the umbilical stump, in some neonates. Metastatic foci
of infection can follow bacteremia and can involve the
lungs, kidney, spleen, bones, or CNS.
Most cases of neonatal meningitis result from bacteremia.
Fetal meningitis followed by stillbirth [344] or
hydrocephalus, presumably because of maternal bacteremia
and transplacentally acquired infection, has been
described, but is exceedingly rare. Although CSF leaks
caused by spiral fetal scalp electrodes do occur, no cases
of meningitis have been traced to this source [345,346].
After delivery, the meninges can be invaded directly from
an infected skin lesion, with spread through the soft tissues
and skull sutures and along thrombosed bridging
veins [315], but in most circumstances, bacteria gain
access to the brain through the bloodstream to the choroid
plexus during the course of sepsis [344]. Infants with
developmental defects, such as a midline dermal sinus or
myelomeningocele, are particularly susceptible to invasion
of underlying nervous tissue [23].
Brain abscesses can result from hematogenous spread
of microorganisms (i.e., septic emboli) and proliferation
in tissue that is devitalized because of anoxia or vasculitis
with hemorrhage or infarction. Certain organisms are
more likely than others to invade nervous tissue and cause
local or widespread necrosis [23]. Most cases of meningitis
related to C. koseri (formerly C. diversus) and E. sakazakii
are associated with formation of cysts and abscesses.
Other gram-negative bacilli with potential to cause brain
abscesses include Proteus, Citrobacter, Pseudomonas, S. marcescens,
and occasionally GBS [155,166,347–349]. Volpe
[350] commented that bacteria associated with brain
abscesses are those that cause meningitis with severe
vasculitis.
HOST FACTORS PREDISPOSING TO
NEONATAL BACTERIAL SEPSIS
Infants with one or more predisposing factors (e.g., low
birth weight, premature rupture of membranes, septic or
traumatic delivery, fetal hypoxia, maternal peripartum
infection) are at increased risk for sepsis. Microbial factors
such as inoculum size [351] and virulence properties of
the organism [310] undoubtedly are significant. Immature
function of phagocytes and decreased inflammatory and
immune effector responses are characteristic of very small
CHAPTER 6 Bacterial Sepsis and Meningitis
243
infants and can contribute to the unique susceptibility of
the fetus and newborn (see Chapter 4).
Metabolic factors are likely to be important in increasing
risk for sepsis and severity of the disease. Fetal
hypoxia and acidosis can impede certain host defense
mechanisms or allow localization of organisms in
necrotic tissues. Infants with hyperbilirubinemia can have
impairment of various immune functions, including
neutrophil bactericidal activity, antibody response, lymphocyte
proliferation, and complement functions (see
Chapter 4). Indirect hyperbilirubinemia that commonly
occurs with breast-feeding jaundice rarely is associated
with neonatal sepsis [352]. Late-onset jaundice and direct
hyperbilirubinemia can be the result of an infectious process.
In one study from Turkey, more than one third of
infants with late-onset direct hyperbilirubinemia had culture-proven
sepsis, with gram-negative enteric bacteria
including E. coli the most common etiologic agent [353].
Evidence of diffuse hepatocellular damage and bile stasis
has been described in such infected and jaundiced infants
[354,355].
Hypothermia in newborns, generally defined as a rectal
temperature equal to or less than 35 C( 95 F), is associated
with a significant increase in the incidence of sepsis,
meningitis, pneumonia, and other serious bacterial
infections [356–359]. In developing countries, hypothermia
is a leading cause of death during the winter.
Hypothermia frequently is accompanied by abnormal leukocyte
counts, acidosis, and uremia, each of which can
interfere with resistance to infection. The exact cause of
increased morbidity in infants presenting with hypothermia
is poorly understood, however. In many infants, it is
unclear whether hypothermia predisposes to or results
from bacterial infection. In a large outbreak of S. marcescens
neonatal infections affecting 159 cases in Gaza City,
Palestine, hypothermia was the most common presenting
symptom, recorded in 38% of cases [360].
Infants with galactosemia have increased susceptibility
to sepsis caused by gram-negative enteric bacilli, in particular
E. coli [361–363]. Among eight infants identified
with galactosemia by routine newborn screening in
Massachusetts, four had systemic infection caused by
E. coli [362]. Three of these four infants died of sepsis
and meningitis; the fourth infant, who had a urinary tract
infection, survived. A survey of state programs in which
newborns are screened for galactosemia revealed that
among 32 infants detected, 10 had systemic infection,
and 9 died of bacteremia. E. coli was the infecting organism
in nine of the infants. Galactosemic neonates seem
to have an unusual predisposition to severe infection with
E. coli, and bacterial sepsis is a significant cause of death
among these infants. Depressed neutrophil function
resulting from elevated serum galactose levels is postulated
to be a possible cause of their predisposition to sepsis
[364,365]. The gold standard for diagnosis of classic
galactosemia is measurement of galactose-1-phosphate
uridyltransferase activity in erythrocytes, and the sole
therapy is galactose restriction in the diet [366]. Shurin
[364] observed that infants became ill when serum galactose
levels were high when glucose levels were likely to
be low, and that susceptibility to infection diminished
when dietary control was initiated.